We have studied the toxicology of cigarette smoke, particularly with regard to the free radicals in smoke. (Our initial research was funded Grant HL-16029.) We now wish to broaden our study to include tobacco smoke from all types of cigarettes, cigars, and pipes, and also the exhaust from gasoline and diesel powered automobiles. The combustion of all organic materials in air produces free radicals; furthermore, radicals are toxic and have sufficient reactivity to be responsible for at least some of the pulmonary pathology caused by smoke. In our work to date we have developed electron spin resonance methods (ESR) and ESR spin trap methods to study the radicals produced by smoke. We find for the first time, that there are two populations of radicals in smoke: a reactive, largely oxygen-centered set of radicals in the gas phase, and a set of longer lived and less reactive radicals in tar. We suggest the former are RO. and ArCO 2. radicals, and the tar radicals may be a polyphenoxy radical similar to the stable radicals in melanin pigments. The number of radicals per puff in cigarette smoke is remarkably large: more than 10 to the 15th power radicals/puff, with about equal numbers in the gas phase and the tar. There also are approximtely the same number of radicals in mainstream and sidestream smoke. We propose to: identify the concentrations and the structures of the radicals in smoke from various environmental sources, including cigarettes, cigars and pipes, and both gasoline and diesel exhausts; to study the chemical reactivity of the radicals in smoke using systems that model biological target tissues; and to initiate both animal and human studies to attempt to relate the radical reactivity in smoke to the pathology caused by smoke.